West Nile virus outbreak in captive and wild raptors,Czech Republic, 2018

West Nile virus lineage 2 (WNV‐2) was detected in the brain of 17 goshawks (Accipiter gentilis) that succumbed to neuroinvasive disease in the Czech Republic during 2018: twelve birds were captive and five wild. Furthermore, two wild sparrowhawks (Accipiter nisus) and three other captive birds of prey (golden eagle Aquila chrysaetos, hybrid saker falcon Falco cherrug × F. rusticolus and Harris's hawk Parabuteo unicinctus) also died due to WNV encephalitis. The 2018 outbreak in Czech raptors clearly reflects a new epidemiological situation and indicates an increasing risk of both raptor and human infection with WNV‐2 in the country.     

Variation in Vitamin E,Glutathione Peroxidase and Retinol Concentrations in Blood Plasma of Primiparous Sows and their Piglets,and in Vitamin E,Selenium and Retinol Contents in Sows' Milk

The concentrations of vitamin E, glutathione peroxidase (GSH-Px) and retinol were analysed in blood plasma of six primiparous sows during gestation and lactation and in their suckling piglets, and the concentrations of vitamin E, selenium and retinol were analysed in colostrum and in sows' milk. During late gestation the concentrations of vitamin E and retinol in blood plasma increased slowly while no changes were found for GSH-Px. This was followed by a large decline on the day of farrowing, when the lowest mean values of 1.07 mg, 0.15 mg and 2879 U per litre (l) of blood plasma, respectively, were recorded. During lactation the concentrations of vitamin E, GSH-Px and retinol in blood plasma of the sows increased to levels observed during late gestation. The highest mean concentrations of vitamin E (17.9 mg kg- 1 ), selenium (200 w g l- 1 ) and retinol (2.45 mg kg- 1 ) were found in colostrum, but with a large variation between sows. One week postpartum the concentrations of vitamin E, selenium and retinol in sow milk had decreased, on average by 86, 68 and 71%, respectively, after which only small changes occurred. Mean concentrations of vitamin E (1.77 mg l- 1 ), GSH-Px (682 U l- 1 ) and retinol (0.07 mg l- 1 ) were low in the blood plasma of the piglets at birth, but a large increase was observed on the next sampling occasion at the age of 3 days (vitamin E: 5.31 mg l- 1 ; GSH-Px: 996 U l- 1 ; retinol: 0.19 mg l- 1 ). The mean concentration of vitamin E in blood plasma of the piglets declined thereafter until the age of 6 weeks (1.04 mg l- 1 ), when there was a small increase, while the mean concentrations of GSH-Px and retinol continued to increase during the suckling period. A high correlation was found between the concentration of vitamin E in blood plasma and sidefat thickness of the sows (r = 0.94), and between the concentration of vitamin E in colostrum and vitamin E in blood plasma of the sows on the day of farrowing (r =0.77). High correlations were also found between the concentration of vitamin E in the blood plasma of the piglets at 3 days and 5 weeks of age and the concentration of vitamin E in colostrum (r = 0.78) and (r =0.89), respectively. The results indicate that vitamin E storage in the adipose tissues of the sow has a great influence on the supply of vitamin E via colostrum and milk to the piglet.     

An association between the level of oxidative stress and the concentrations of NEFA and BHBA in the plasma of ketotic dairy cows

The aim of this study was to evaluate the oxidative status in ketotic cows. We observed changes in the oxidative status and correlations between the oxidative and metabolic status in non‐ketotic (n = 10), subclinical ketotic (n = 10) and ketotic cows (n = 10). Plasma samples were analysed by standard biochemical techniques and ELISA to determine traditional metabolic parameters: triglyceride (TG), phosphonium (P), calcium (Ca), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), immune globulin (Ig), total cholesterol (TC), high‐density lipoprotein (HDL), very low‐density lipoprotein (VLDL) and lactate dehydrogenase (LDH); energy metabolism indices: glucose, β‐hydroxybutyrate (BHBA) and non‐esterified fatty acids (NEFA); and indices of oxidative status: malondialdehyde (MDA), hydrogen peroxide (H₂O₂), vitamin C, vitamin E, superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), catalase (CAT), xanthine oxidase (XOD) and total antioxidant capacity (TAOC). The results of this study showed that plasma glucose levels were lower in ketotic and subclinical ketotic cows than in non‐ketotic cows; however, the plasma NEFA and BHBA concentrations were higher. In addition, significant decreases in TC, HDL and VLDL and significant increases in AST, ALT and LDH were observed in the plasma of the ketotic cows. The ketotic cows showed decreased plasma SOD, CAT, vitamin C and vitamin E, inhibited hydroxyl radical capacity and increased plasma H₂O₂ and MDA. There were positive correlations between the plasma NEFA and ALT, AST, LDH and MDA and negative correlations between the plasma NEFA and TC, HDL, VLDL, SOD, vitamin C, vitamin E, 1542280 uric acid and inhibited hydroxyl radical capacity. In addition, there were positive correlations between BHBA concentrations and ALT, AST and LDH and negative correlations between plasma BHBA concentrations and TC, HDL, VLDL, vitamin E and inhibited hydroxyl radical capacity. Overall, ketotic dairy cows experience oxidative stress, which is presumably associated with hyperketonemia and higher NEFA.     

Retinol Values in the Plasma of the Arabian Camel (Camelus dromedarius) and the Influence of Aflatoxicosis

The normal values are reported of the concentration of vitamin A (retinol) in the plasma of 44 male and female adult camels (Camelus dromedarius) in the United Arab Emirates. The concentrations of the vitamin in the plasma of eight camels of both sexes afflicted with aflatoxicosis were also determined. The mean concentration (±SD) of the vitamin in healthy camels was 460.1±49.3 ng/L. Sex had no significant effect on the concentration of the vitamin. Camels with aflatoxicosis had a mean concentration of retinol in the plasma of 243.4±32.3 ng/L. The concentrations of aflatoxins in the liver and ruminal contents of these animals were 18.2±1.3 and 243.4 g/kg, respectively.     

Expression of genes related to liver fatty acid metabolism in fat‐tailed and thin‐tailed lambs during negative and positive energy balances

Fat‐tailed sheep breeds can tolerate periods of negative energy balance without suffering from elevated concentration of plasma non‐esterified fatty acid (NEFA). This ability was attributed to unique metabolism of fat‐tailed adipose depot, whereas role of liver as an influential organ in fatty acid metabolism was not evaluated yet. Hence, current study was conducted to evaluate the effects of negative and positive energy balances on liver expression of genes related to fatty acid metabolism in fat‐tailed and thin‐tailed lambs. Lambs experienced negative (21 days) and positive (21 days) energy balances and were slaughtered at the beginning and end of negative energy balance and at the end of positive energy balance. Real‐time quantitative polymerase chain reaction (RT‐Q‐PCR) was conducted to evaluate changes in gene expression. Expression of diglyceride acyltransferase 1 (DGAT1), 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2 (HMGCS2) and apolipoprotein B (APOB) was not affected by genotype, energy balance and their interaction. Expression of carnitine palmitoyltransferase 1 (CPT1) was significantly higher in liver of fat‐tailed comparing to thin‐tailed lambs regardless of energy balance (p < 0.02). Catalase mRNA abundance was increased in response to negative energy balance (p < 0.02), and severity of this enhancement was higher in fat‐tailed lambs (p < 0.06). Expression of CPT1 was positively correlated with expression of HMGCS2 in both fat‐tailed (p < 0.05) and thin‐tailed lambs (p < 0.002); however, the correlation was weaker in fat‐tailed lambs (0.72 vs. 0.57, respectively, for thin‐tailed and fat‐tailed lambs). There was a positive correlation between DGAT1 and APOB genes expression in fat‐tailed lambs (0.94; p < 0.001), whereas this correlation was not observed in thin‐tailed lambs. Results demonstrate that liver of fat‐tailed lambs has higher capacity for metabolism of mobilized NEFA exposed to liver during negative energy balance.     

Annual survival and site fidelity of free‐ranging white‐tailed deer (Odocoileus virginianus): comparative demography before (1983–1992) and after (1993–2005) spatial confinement

Survival and movement are important demographic variables influencing the dynamics of large herbivores with implications for management and evolution of life‐history strategies. Management practices such as spatial confinement and harvest regulation attempt to control survival and movement for the sustainability of harvested deer populations, but a paucity of long‐term data exists on these management practices. We examined annual survival and site fidelity of free‐ranging white‐tailed deer (Odocoileus virginianus) over 10 years (1983–1992) to compare demographic parameters after spatial confinement (1993–2005). We used capture records (n = 174; 104 females, 70 males), marked deer recaptures (n = 42), and dead recoveries (n = 68) to estimate sex‐specific, age‐specific and time‐specific parameters. We found that annual female survival was 50% from 1983–1987 during a period of intense harvest, but increased to 93.7% after intense harvesting was eliminated. Prior to spatial confinement, annual survival of marked male deer averaged 36.7%–42.5%. After spatial confinement, annual survival increased on average for males (58%–99%) and females (77%–98%). Females showed high levels of site fidelity (>99%) prior to spatial confinement, whereas males showed much less site fidelity (≤4.5% for the 2 top‐ranking models). During spatial confinement, the semi‐impermeable fence effectively increased site fidelity of males (≥56%). These results stem from long‐term study (23 years) of a large herbivore experiencing changes to life‐history, resulting from changes in management that were applied to the population and aimed at altering population demographics, for sustainability of a harvestable population of deer.     

Pharmacokinetics of tildipirosin in porcine plasma,lung tissue,and bronchial fluid and effects of test conditions on in vitro activity against reference strains and field isolates of Actinobacillus pleuropneumoniae

Rose, M, Menge, M, Bohland, C, Zschiesche, E, Wilhelm, C, Kilp, S, Metz, W, Allan, M, Röpke, R, Nürnberger, M Pharmacokinetics of tildipirosin in porcine plasma, lung tissue, and bronchial fluid and effects of test conditions on in vitro activity against reference strains and field isolates of Actinobacillus pleuropneumoniae. J. vet. Pharmacol. Therap.  36 , 140–153. The pharmacokinetics of tildipirosin (Zuprevo^® 40 mg/mL solution for injection for pigs), a novel 16‐membered‐ring macrolide for the treatment for swine respiratory disease (SRD), was investigated in studies collecting blood plasma and postmortem samples of lung tissue and bronchial fluid (BF) from swine. In view of factors influencing the in vitro activity of macrolides, and for the interpretation of tildipirosin pharmacokinetics in relation to minimum inhibitory concentrations (MIC), additional experiments were conducted to study the effects of pH, carbon dioxide‐enriched atmosphere, buffers, and serum on tildipirosin MICs for various reference strains and Actinobacillus (A.) pleuropneumoniae field isolates. After single intramuscular (i.m.) injection at 4 mg/kg body weight, maximum plasma concentration (C_max) was 0.9 μg/mL observed within 23 min (T_max). Mean residence time from the time of dosing to the time of last measurable concentration (MRT_last) and terminal half‐life (T_1/2) both were about 4 days. A dose–response relationship with no significant sex effect is observed for area under the plasma concentration–time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUC_last) over the range of doses up to 6 mg/kg. However, linear dose proportionality could not be proven with statistical methods. The time–concentration profile of tildipirosin in BF and lung far exceeded that in blood plasma. In lung, tildipirosin concentrations reached 3.1 μg/g at 2 h, peaked at 4.3 μg/g at day 1, and slowly declined to 0.8 μg/g at day 17. In BF, tildipirosin levels were 14.3, 7.0, and 6.5 μg/g at days 5, 10, and 14. T_1/2 in lung was ～7 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination. Culture media pH and carbon dioxide‐enriched atmosphere (CO₂‐EA) had a marked impact on in vitro activity of tildipirosin in reference strains of various rapidly growing aerobic and fastidious bacteria including Histophilus (H.) somni ATCC 700025 and A. pleuropneumoniae ATCC 27090. For A. pleuropneumoniae ATCC 27090 testing conditions without CO₂‐EA resulted in reduced acidification of culture media pH and a reduction in the minimum inhibitory concentrations compared to standard in vitro test conditions by 2 log₂ dilution steps (4‐fold) from 8 to 2 μg/mL. Supplementary buffering of standard culture media resulted in a reduction in the A. pleuropneumoniae (n = 8) MIC range by 4 log₂ dilution steps (16‐fold) from 8–16 to 0.5–1 μg/mL. Incremental supplementation of culture media with 50% serum resulted in noticeable shifts to lower minimum or maximum MICs by at least 2 log₂ dilution steps (≥4‐fold) in all aerobic and fastidious reference strains tested except for Pasteurella (P.) multocida. The MIC of A. pleuropneumoniae ATCC 27090 decreased by 2–4 log₂ dilution steps (4 to 16‐fold) from 8 to 0.5–2 μg/mL when 50% serum was added to the standard assay. Considering a higher presence of serum and the rather neutral pH conditions maintained in vivo, it is suggested to take the influence of these factors on in vitro activity into account when interpreting tildipirosin MICs for A. pleuropneumoniae in relation to pharmacokinetics.     

Vaccination with Mycobacterium bovis BCG Strains Danish and Pasteur in White‐tailed Deer (Odocoileus virginianus) Experimentally Challenged with Mycobacterium bovis

Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis in domestic livestock and the cause for many faltering bovine tuberculosis eradication programmes. One approach in dealing with wildlife reservoirs of disease is to interrupt inter‐species and intraspecies transmission through vaccination of deer or cattle. To evaluate the efficacy of BCG vaccination in white‐tailed deer, 35 deer were assigned to one of three groups; one s.c. dose of 10⁷ CFU of M. bovis BCG Pasteur (n = 12); 1 s.c. dose of 10⁷ CFU of M. bovis BCG Danish (n = 11); or unvaccinated deer (n = 12). After vaccination, deer were inoculated intratonsilarly with virulent M. bovis. Lesion severity scores of the medial retropharyngeal lymph node, as well as all lymph nodes combined, were reduced in vaccinated deer compared to unvaccinated deer. BCG Danish vaccinated deer had no late stage granulomas characterized by coalescent caseonecrotic granulomas containing numerous acid‐fast bacilli compared to BCG Pasteur vaccinated or unvaccinated deer where such lesions were present. Both BCG strains were isolated as late as 250 days after vaccination from deer that were vaccinated but not challenged. In white‐tailed deer, BCG provides protection against challenge with virulent M. bovis. Issues related to vaccine persistence, safety and shedding remain to be further investigated.     

Effect of feeding rice whole crop silage on growth rate,levels of vitamin A, β‐carotene,vitamin E and IGF‐1 in plasma and skeletal muscle protein degradation in Japanese black calves

This study evaluated the effects of rice whole crop silage (RWCS) on growth, plasma levels of vitamin A, β‐carotene, vitamin E and IGF‐1, and expression of genes involved in muscle protein degradation and synthesis in Japanese Black calves. Eleven calves were divided into RWCS (fed RWCS ad libitum and concentrate, n = 5) and control groups (fed hay ad libitum and concentrate, n = 6). Final body weight and dairy gain were significantly larger in the RWCS group compared with the control group. Plasma β‐carotene and vitamin E concentrations were significantly higher in the RWCS group compared with control group. Although plasma vitamin E concentration in the RWCS group significantly increased from 4 to 9 months of age, it did not increase in the control group. At 6 months of age in the RWCS group, ubiquitin B (p < 0.05) and calpain 1 (p = 0.097) mRNA expression were lower than control group, but they were not different between groups at 9 months of age. These results indicate that RWCS increases plasma β‐carotene level and promotes muscle growth because of a decrease in the rate of protein degradation, but the effect is lost with the increase in plasma vitamin E level.     

Semiquantitative multi‐analysis of plasma obtained from Romney lambs (Ovis aries) by inductively coupled plasma mass spectrometry,and the classification according to feed type

The establishment of a classification system for domestic animals on consumed feed stuff is thought to be important from both a hygiene and market point of view. We collected plasma samples of Romney lambs (Ovis aries) which were fed one of the following: a herb‐clover mix (n = 10) which included chicory, red clover, white clover and plantain; a plant‐grass mix (n = 10) which included plantain, ryegrass and white clover; or a grass mix (n = 10) which included ryegrass and white clover. A total of 20 elements in plasma samples obtained from the lambs were analyzed using inductively coupled plasma mass spectrometry. The data were then analyzed by principal component analysis. The lambs were divided into three groups on a score plot depending on the different feed conditions. Furthermore, discriminant analyses of the elements were examined, using linear discriminant analysis with forward stepwise regression. This discriminant function correctly classified the samples from each group. The accuracy of classification of each group, as shown by 10‐fold cross‐validation, proved the effectiveness of the established discriminant function. It is concluded that using linear discriminant analysis might be a useful tool for the validation of elements from plasma in lambs grown in different conditions.     

Plasma thiobarbituric acid reactive substances,vitamin A and vitamin E levels and resumption of postpartum ovarian activity in dairy cows

Vitamins with antioxidative functions are commonly used as supplements to improve fertility in dairy cows. However, according to field test results uncertainty exists about the effect of these vitamins, especially in vitamin A and vitamin E, on ovarian functional activity. This study was performed to reveal the physiological characteristics of cows receiving enough feed and the ovaries of which were activated in the early postpartum period. Six of 12 primiparous cows showing the corpus luteum on 25 to 27 days after parturition were classified as early responders (PER); the remaining six were classified as late responders (PLR). Among 11 multiparous cows, nine were early responders (MER), and the remaining two were late responders (MLR). Plasma concentration of thiobarbituric acid reactive substances (TBARS) in the PER were lower than those in the PLR (P < 0.01). The ratio of plasma all‐trans‐retinol to intake α‐tocopherol or β‐carotene were increased in the following order: MER < PER < PLR (P < 0.01). The milk lactose (P < 0.025) and plasma glucose (P < 0.01) of the early responders tended to be lower than those of the late responders. These may have been associated with the availability of vitamins or energy balance. Thus, we suggest the possibility that the cows which were able to utilize antioxidants and energy from the feed efficiently may have earlier resumption of ovaries postpartum.     

Pharmacokinetics of tildipirosin in bovine plasma,lung tissue,and bronchial fluid (from live,nonanesthetized cattle)

Menge, M., Rose, M., Bohland, C., Zschiesche, E., Kilp, S., Metz, W., Allan, M., Röpke, R., Nürnberger, M. Pharmacokinetics of tildipirosin in bovine plasma, lung tissue, and bronchial fluid (from live, nonanesthetized cattle). J. vet. Pharmacol. Therap.  35 , 550–559. The pharmacokinetics of tildipirosin (Zuprevo^® 180 mg/mL solution for injection for cattle), a novel 16‐membered macrolide for treatment, control, and prevention of bovine respiratory disease, were investigated in studies collecting blood plasma, lung tissue, and in vivo samples of bronchial fluid (BF) from cattle. After single subcutaneous (s.c.) injection at 4 mg/kg body weight, maximum plasma concentration (C_max) was 0.7 μg/mL. T_max was 23 min. Mean residence time from the time of dosing to the time of last measurable concentration (MRT_last) and terminal half‐life (T_1/2) was 6 and 9 days, respectively. A strong dose–response relationship with no significant sex effect was shown for both C_max and area under the plasma concentration–time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUC_last) over the range of doses up to 6 mg/kg. Absolute bioavailability was 78.9%. The volume of distribution based on the terminal phase (V_z) was 49.4 L/kg, and the plasma clearance was 144 mL/h/kg. The time–concentration profile of tildipirosin in BF and lung far exceeded those in blood plasma. In lung, tildipirosin concentrations reached 9.2 μg/g at 4 h, peaked at 14.8 μg/g at day 1, and slowly declined to 2.0 μg/g at day 28. In BF, the concentration of tildipirosin reached 1.5 and 3.0 μg/g at 4 and 10 h, maintained a plateau of about 3.5 μg/g between day 1 and 3, and slowly declined to 1.0 at day 21. T_1/2 in lung and BF was approximately 10 and 11 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination.     

Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs

Bimazubute, M., Cambier, C., Baert, K., Vanbelle, S., Chiap, P., Gustin, P. Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs. J. vet. Pharmacol. Therap. 34 , 176–183. The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)‐administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra‐high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter‐dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 μg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (μg/mL) can be predicted taking into account the OTC concentrations in plasma (μg/mL), according to the following equation: OTC_{nasal secretions} = 0.28 OTC_plasma?1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single‐dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. The data collected in 10 pigs for OTC were subjected to non‐compartmental analysis. In plasma, the maximum concentration of drug (C_max), the time at which this maximum concentration of drug (T_max) was reached, the elimination half‐life (t½) and the area under the concentration vs. time curve (AUC) were, respectively, 19.4 μg/mL, 4.0, 5.1 h and 150 μg·h/mL. In nasal secretions, C_max, T_max, t½ and AUC were, respectively, 6.29 μg/mL, 4.0, 6.6 h and 51.1 μg·h/mL.     

Pharmacokinetic studies of flunixin meglumine and phenylbutazone in plasma,exudate and transudate in sheep

Flunixin meglumine (FM, 1.1 mg/kg) and phenylbutazone (PBZ, 4.4 mg/kg) were administered intravenously (i.v.) as a single dose to eight sheep prepared with subcutaneous (s.c.) tissue-cages in which an acute inflammatory reaction was stimulated with carrageenan. Pharmacokinetics of FM, PBZ and its active metabolite oxyphenbutazone (OPBZ) in plasma, exudate and transudate were investigated. Plasma kinetics showed that FM had an elimination half-life (t_½β) of 2.48 ± 0.12 h and an area under the concentration – time curve (AUC) of 30.61 ± 3.41 μg/mL.h. Elimination of PBZ from plasma was slow (t_½β = 17.92 ± 1.74 h, AUC = 968.04 ± μg/mL.h.). Both FM and PBZ distributed well into exudate and transudate although penetration was slow, indicated by maximal drug concentration (C_max) for FM of 1.82 ± 0.22 μg/mL at 5.50 ± 0.73 h (exudate) and 1.58 ± 0.30 μg/mL at 8.00 h (transudate), and C_max for PBZ of 22.32 ± 1.29 μg/mL at 9.50 ± 0.73 h (exudate) and 22.07 ± 1.57 μg/mL at 11.50 ± 1.92 h (transudate), and a high mean tissue-cage fluids:plasma AUC_last ratio obtained in the FM and PBZ groups (80–98%). These values are higher than previous reports in horses and calves using the same or higher dose rates. Elimination of FM and PBZ from exudate and transudate was slower than from plasma. Consequently the drug concentrations in plasma were initially higher and subsequently lower than in exudate and transudate.     

Administration of RRR‐α‐tocopherol to pregnant mares stimulates maternal IgG and IgM production in colostrum and enhances vitamin E and IgM status in foals

This study assessed the effect of a vitamin E supplement given to pregnant mares on immunoglobulins (Ig) levels in foals. In addition, the fatty acid (FA) content and composition of the mares’ milk was assessed. Milk α‐tocopherol concentrations were compared between pregnant Danish Warmblood mares (n = 17) given a daily oral supplement of 2500 international units (IU) RRR‐α‐tocopherol in the last 4 weeks of pregnancy and a group of unsupplemented mares (n = 17) receiving 170–320 IU vitamin E daily originating from the feed. Milk α‐tocopherol was higher in supplemented mares (36.7, 12.4 and 9.8 μmol/l respectively) in relation to control mares (13.1, 6.4 and 5.8 μmol/l on days 1, 2 and 3 respectively; p < 0.001). Milk IgG was higher on days 2 and 3 post‐partum (PP) in supplemented mares (1.03 and 0.73 mg/ml respectively) in relation to control mares (0.79 and 0.56 mg/ml respectively; p < 0.05). Milk IgM was higher on days 2 and 3 post‐partum (PP) in supplemented mares (0.19 and 0.17 mg/ml) in relation to control mares (0.13 and 0.11 mg/ml respectively; p < 0.05). Plasma α‐tocopherol in foals was higher from supplemented mares on days 1, 2 and 3 (5.7, 14.8 and 19.2 μmol/l respectively) in relation to foals from control mares (3.6, 6.1 and 7.6 respectively; p < 0.001). Foal plasma IgM was higher from supplemented mares on day 3 (0.50 mg/ml) in relation to foals from control mares (0.32 mg/ml; p < 0.001). The total FA content in milk was highest on day 1 (21.6 g FA/kg milk) in relation to days 2 and 3 (13.6 and 13.5 g FA/kg milk respectively; p < 0.001). In conclusion, a daily oral supplement of 2500 IU RRR‐α‐tocopherol increased α‐tocopherol content in mare milk and foal plasma, IgG and IgM in mare milk and IgM in foal plasma.     

Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous,subcutaneous and oral administration

The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high‐performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (V_z) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (V_ss) of 0.22 ± 0.12 L/kg. Median plasma terminal half‐life (t_1/2) was 1.19 h (range 0.71–1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C_max 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4–8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5‐hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate.     

Effects of exposure to artificial long days on milk yield,maternal insulin‐like growth factor 1 levels and kid growth rate in subtropical goats

This study was designed to determine whether any relationship exists between exposure to artificial long days, milk yield, maternal plasma insulin‐like growth factor 1 (IGF‐1) levels, and kid growth rate in goats. One group of lactating goats was maintained under naturally decreasing day length (control group; n = 19), while in another one, they were kept under artificial long days (LD group; n = 19). Milk yield was higher in goats from the LD group than that in the control group (P < 0.05). Maternal IGF‐1 levels at day 57 of lactation were higher (P < 0.05) in goats from the LD group than the levels in the control group and were positively correlated with the total milk yields per goat at days 43 and 57 of lactation (r = 0.77 and r = 0.84, respectively; P < 0.01). Daily weight gain at week 4 was higher (P < 0.01) in kids from the LD group than that in kids from the control group and was correlated with total and average IGF‐1 maternal levels (r = 0.60 and r = 0.60, P < 0.05). It was concluded that submitting lactating goats to artificial long days increases milk yield, plasma IGF‐1 maternal levels and the growth rate of the kids.     

UV‐light and dietary vitamin D and their effects on ionized calcium and 25‐OH‐D plasma concentrations in captive gentoo penguins (Pygoscelis papua)

In this study, the effect of ultraviolet (UV) light and dietary vitamin D on calcium metabolism in permanently indoor‐housed gentoo penguins (Pygoscelis papua ) was investigated. The study consisted of three periods, each completed with blood samples to analyse plasma concentrations of 25‐OH‐D, 1,25‐(OH)₂‐D, ionized (iCa) and total calcium (tCa). During the first study period (D), animals were housed under routine conditions without UV‐light and fed a diet of different fish species, supplemented with 1,000 IU vitamin D per animal and day. The following study period (Baseline) of 28‐day duration consisted of the same diet without any vitamin D supplementation and without UV‐light. During the study period (UVB) artificial UV‐light was added for 3 weeks. The vitamin D content of fish was measured by high‐performance liquid chromatography. It varied between fish species and between facilities, ranging from no measurable content in capelin (Mallotus villosus ) to 7,340 IU vitamin D/kg original matter (OM) in herring (Clupea spp). The average dietary vitamin D content was 311 IU/kg OM at facility 1 and 6,325 IU/kg OM at facility 2, resulting in a vitamin D intake per animal and day without supplementation of 130 IU (25.5 IU/kg body weight BW) and 2,454 IU (438.2 IU/kg BW) respectively. The supplementation of vitamin D elevated significantly the plasma concentrations of 25‐OH‐D by an intraindividual difference of 15 (range ?2 to 59) nmol/L and tCa by 0.1 (0.0–0.3) mmol/L only at facility 2. The exposure to UV‐light raised the blood concentrations of tCa at facility 2 by 0.15 (0.1–0.2) mmol/L, and of iCa and tCa for females at facility 1 by 0.23 (0.13–0.41) mmol/L and 1.8 (1.1–2.5) mmol/L respectively. No significant influence of the study periods (D) and (UVB) was found for the concentrations of 1,25‐(OH)₂‐D at both facilities.     

No detectable carotenoid concentrations in serum of llamas and alpacas

Carotenoids are lipid‐soluble pigments and important for a variety of physiological functions. They are major dietary vitamin A precursors and act as lipophilic antioxidants in a variety of tissues and are associated with important health benefits in humans and animals. All animals must acquire carotenoids from their diet, but to our knowledge, there are no studies investigating the intestinal carotenoid absorption and their blood concentrations in New World camelids. The present study aimed to assess the serum concentrations of selected carotenoids in llamas (n = 13) and alpacas (n = 27). Serum carotenoids as well as retinol (vitamin A) and α‐tocopherol (vitamin E) were determined by high‐performance liquid chromatography coupled with mass spectrometry and these were unable to detect any carotenoids (α‐ and β‐carotene, α‐ and β‐cryptoxanthin, lutein, zeaxanthin, lycopene) in the samples. The concentrations of retinol in alpacas (2.89 ± 1.13 μmol/l; mean ± SD) were higher (p = 0.024) than those found in llamas (2.05 ± 0.87 μmol/l); however, the concentrations of α‐tocopherol were not significantly (p = 0.166) different (llamas: 3.98 ± 1.83 μmol/l; alpacas: 4.95 ± 2.14 μmol/l). The results show that both llamas and alpacas are not able to absorb intact carotenoids, but efficiently convert provitamin A carotenoids to retinol.     

Pharmacokinetics and toxicity of the novel oral demethylating agent zebularine in laboratory and tumor bearing dogs

The purpose of this study was to determine the plasma pharmacokinetics (PK) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by HPLC‐MS/MS following an oral zebularine dose of 8 or 4 mg kg^?1. Plasma zebularine clearance was constant. Mean maximum concentration (C_max) was 23 ± 4.8 and 8.6 ± 1.4 µM following 8 and 4 mg kg^?1, respectively. Mean half‐life was 5.7 ± 0.84 and 7.1 ± 2.1 following 8 and 4 mg kg^?1, respectively. A single 8 mg kg^?1 dose was well tolerated. Daily 4 mg kg^?1 treatment in three laboratory dogs resulted in grade 4 neutropenia (n = 3), grade 1 anorexia (n = 2) and grade 1 or 2 dermatologic changes (n = 2). All adverse events resolved with supportive care. A 4 mg kg^?1 dose every 21 days was well tolerated. A follow‐up dose escalation study is in progress with a lower starting dose.